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  • NARCIS (Royal Netherlands Academy of Arts and Sciences)  (9)
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  • 1
    In: Clinical Endocrinology, January 2014, Vol.80(1), pp.65-72
    Description: Byline: Mireille N. M. Poppel, Willibald Zeck, Daniela Ulrich, Eva-Christina Schest, Birgit Hirschmugl, Uwe Lang, Christian Wadsack, Gernot Desoye Summary Objective Chemerin is a novel adipokine implicated in inflammation and obesity. We hypothesized that foetal chemerin would be elevated in gestational diabetes mellitus (GDM) and correlate with foetal and maternal adiposity. Design Observational, longitudinal study. Subjects and measurements Foetal chemerin was measured separately in arterial and venous cord blood of 30 infants born to mothers with (n = 15) and without GDM (n = 15), in their mothers in early third trimester and at delivery and in amniotic fluid (week 32) of women with GDM. Expression of chemerin and its receptor in human foetal tissues commercially available and in placental cells was measured by quantitative PCR. Associations between foetal and maternal anthropometric and metabolic variables were assessed in multivariate regression models. Results In GDM, foetal arterial but not venous cord blood chemerin levels were elevated by about 60% (P 0ae05). Venous cord blood chemerin was higher in infants of obese women (P 0ae01). In multivariate analyses, neither amniotic fluid nor cord blood chemerin levels correlated with birth weight or ponderal index. Both arterial and venous chemerin levels were related to maternal chemerin at birth, and arterial chemerin was associated with GDM status in addition. Maternal levels were unaltered in GDM, but higher in maternal obesity. Foetal liver produces fourfold more chemerin mRNA than other foetal tissues, whereas its receptor prevails in spleen. Conclusions Based on multivariate analyses, foetal growth appears unrelated to foetal chemerin. Maternal obesity and GDM have differential effects on foetal chemerin levels. Site of major production (liver) and action (spleen) differ in human foetal tissues. Article Note: Equal contribution of both authors.
    Keywords: Obesity -- Analysis ; Gestational Diabetes -- Analysis ; Rna -- Analysis;
    ISSN: 0300-0664
    E-ISSN: 1365-2265
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  • 2
    Description: With the world continuously warming, a mechanistic understanding of how temperature affects interaction strengths, which are fundamental to food-web stability, is needed. As interaction strengths are determined by the flows of energy from resources to consumers, we investigated effects of temperature...
    Keywords: Life Sciences, Medicine And Health Care ; Life Sciences, Medicine And Health Care
    Source: NARCIS (National Academic Research and Collaborations Information System)
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  • 3
    Description: With the world continuously warming, a mechanistic understanding of how temperature affects interaction strengths, which are fundamental to food-web stability, is needed. As interaction strengths are determined by the flows of energy from resources to consumers, we investigated effects of temperature...
    Keywords: Life Sciences, Medicine And Health Care ; Life Sciences, Medicine And Health Care
    Source: NARCIS (National Academic Research and Collaborations Information System)
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  • 4
    Description: With the world continuously warming, a mechanistic understanding of how temperature affects interaction strengths, which are fundamental to food-web stability, is needed. As interaction strengths are determined by the flows of energy from resources to...
    Keywords: Life Sciences, Medicine And Health Care ; Life Sciences, Medicine And Health Care
    Source: NARCIS (National Academic Research and Collaborations Information System)
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  • 5
    Description: Living organisms are constrained by both resource quantity and quality. Ecological stoichiometry offers important insights into how the elemental composition of resources affects their consumers. If resource quality decreases, consumers can respond by...
    Keywords: Life Sciences, Medicine And Health Care ; Life Sciences, Medicine And Health Care
    Source: NARCIS (National Academic Research and Collaborations Information System)
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  • 6
    In: Circulation, 2015, Vol.132(2), pp.82-92
    Description: BACKGROUND—: Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K2P3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K channel–related acid-sensitive K channel-1]) 2-pore-domain K (K2P) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. METHODS AND RESULTS—: Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K2P3.1 subunits exhibited predominantly atrial expression, and atrial K2P3.1 transcript levels were highest among functional K2P channels. K2P3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K2P3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K2P3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. CONCLUSIONS—: Enhancement of atrium-selective K2P3.1 currents contributes to APD shortening in patients with chronic AF, and K2P3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K2P3.1 as a novel drug target for mechanism-based AF therapy.
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0009-7322
    E-ISSN: 15244539
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  • 7
    In: Circulation, 2016, Vol.133(11), pp.e440-e441
    Description: We thank Dr Olschewski and colleagues for their interest in our article,1 and we appreciate their recapitulation of 2 key findings of our work: (1) the identification of increased atrial K2P3.1 (TASK-1) K+ channel expression, I K2P3.1 upregulation, and action potential shortening as substrate in patients with chronic atrial fibrillation (AF); and (2) the presentation of K2P3.1 current inhibition and resulting action potential prolongation as mechanism-based therapeutic paradigm in this subentity of the arrhythmia. Our study focused on the mechanistic contribution of K2P3.1 channels to human atrial electrophysiology and action potential regulation, with particular emphasis on pathophysiological dysregulation in AF. Based on mechanistic data presented in the study, functional correction of atrial ionic remodeling through the suppression of atrial K2P3.1 current emerged as a novel antiarrhythmic option for AF management. We agree with Olschewski et al that efficacy and safety require in-depth preclinical evaluation before transfer of novel therapeutic principles into human application. In their letter, the authors highlight their findings of K2P3.1 expression and functional …
    Keywords: Medicine ; Anatomy & Physiology;
    ISSN: 0009-7322
    E-ISSN: 15244539
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  • 8
    Language: English
    In: Hepatology, March 2004, Vol.39(3), pp.779-791
    Description: Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are characterized by a cholestatic pattern of liver damage, also observed in hereditary or acquired dysfunction of the canalicular membrane transporters bile salt export pump (BSEP, ) and multidrug resistance protein type 3 (MDR3, ). Controversy exists whether a genetically determined dysfunction of BSEP and MDR3 plays a pathogenic role in PBC and PSC. Therefore, 149 healthy Caucasian control individuals (control group) were compared to 76 PBC and 46 PSC patients with respect to genetic variations in and . Sequencing spanned ∼10,000 bp including promoter and coding regions as well as 50–350 bp of flanking intronic regions. In all, 46 and 45 variants were identified in and , respectively. No differences between the groups were detected either in the total number of variants (: control group: 37, PBC: 37, PSC: 31; and : control group: 35; PBC: 32, PSC: 30), or in the allele frequency of the common variable sites. Furthermore, there were no significant differences in haplotype distribution and linkage disequilibrium. In conclusion, this study provides an analysis of and variant segregation and haplotype structure in a Caucasian population. Although an impact of rare variants on BSEP and MDR3 function cannot be ruled out, our data do not support a strong role of and genetic variations in the pathogenesis of PBC and PSC. (H 2004;39:779–791.)
    Keywords: Haplotypes ; ATP Binding Cassette Transporter, Subfamily B -- Genetics ; ATP-Binding Cassette Transporters -- Genetics ; Cholangitis, Sclerosing -- Genetics ; European Continental Ancestry Group -- Genetics ; Liver Cirrhosis, Biliary -- Genetics;
    ISSN: 0270-9139
    E-ISSN: 1527-3350
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  • 9
    Language: English
    Description: Objectives: Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. Methods: HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Results: Of 20 965 patients, 53% presented with latestage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p 〈0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age .50 years (1.46; CI 1.33 to 1.60 vs 30.49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Conclusions: Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥50 years and certain regions in the Netherlands.
    Keywords: Medicine(All)
    ISSN: 2044-6055
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